A mitochondria-specific mutational signature of aging: increased rate of A > G substitutions on the heavy strand.
A mitochondria-specific mutational signature of aging: increased rate of A > G substitutions on the heavy strand.
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DOI：
10.1093/nar/gkac779
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发表时间：
2022-10-14
影响因子：
14.9
通讯作者：
Popadin, Konstantin
中科院分区：
文献类型：
--
作者：
Mikhailova, Alina G.;Mikhailova, Alina A.;Ushakova, Kristina;Tretiakov, Evgeny O.;Iliushchenko, Dmitrii;Shamansky, Victor;Lobanova, Valeria;Kozenkov, Ivan;Efimenko, Bogdan;Yurchenko, Andrey A.;Kozenkova, Elena;Zdobnov, Evgeny M.;Makeev, Vsevolod;Yurov, Valerian;Tanaka, Masashi;Gostimskaya, Irina;Fleischmann, Zoe;Annis, Sofia;Franco, Melissa;Wasko, Kevin;Denisov, Stepan;Kunz, Wolfram S.;Knorre, Dmitry;Mazunin, Ilya;Nikolaev, Sergey;Fellay, Jacques;Reymond, Alexandre;Khrapko, Konstantin;Gunbin, Konstantin;Popadin, Konstantin
线粒体DNA（mtDNA）的突变谱与核基因组的任何已知突变特征都不相似，并且不同生物体之间mtDNA突变谱的变化仍然是不可理解的。由于线粒体负责有氧呼吸，因此预期线粒体DNA突变谱受到氧化损伤的影响。假设氧化损伤随着年龄的增长而增加，我们分析了不同物种的mtDNA突变的世代长度。通过分析不同年龄组的线粒体DNA中成千上万的突变、424种不同世代长度的哺乳动物中70053个同义突变和650个哺乳动物线粒体基因组的同义核苷酸含量，我们发现AH > GH突变的频率在100%~ 100%之间，（H：重链符号）在高世代长度的物种中比低世代长度的物种大两倍，使它们的mtDNA更缺乏AH而富含GH。考虑到AH > GH置换也对mtDNA异步复制过程中的单链时间（TSSS）敏感，我们证明AH > GH置换率是种特异性世代长度和位置特异性TSSS的函数。我们认为AH > GH是与衰老和TSSS相关的氧化损伤的一个特定标志。
The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra between different organisms is still incomprehensible. Since mitochondria are responsible for aerobic respiration, it is expected that mtDNA mutational spectrum is affected by oxidative damage. Assuming that oxidative damage increases with age, we analyse mtDNA mutagenesis of different species in regards to their generation length. Analysing, (i) dozens of thousands of somatic mtDNA mutations in samples of different ages (ii) 70053 polymorphic synonymous mtDNA substitutions reconstructed in 424 mammalian species with different generation lengths and (iii) synonymous nucleotide content of 650 complete mitochondrial genomes of mammalian species we observed that the frequency of AH > GH substitutions (H: heavy strand notation) is twice bigger in species with high versus low generation length making their mtDNA more AH poor and GH rich. Considering that AH > GH substitutions are also sensitive to the time spent single-stranded (TSSS) during asynchronous mtDNA replication we demonstrated that AH > GH substitution rate is a function of both species-specific generation length and position-specific TSSS. We propose that AH > GH is a mitochondria-specific signature of oxidative damage associated with both aging and TSSS.
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人线粒体DNA变异的种群频率高度取决于突变偏差。
影响因子：
2.4
作者：
Dunn CD
通讯作者：
Dunn CD
DNA不匹配修复和氧化DNA损伤：对癌症生物学和治疗的影响。
影响因子：
5.2
作者：
Bridge G;Rashid S;Martin SA
通讯作者：
Martin SA
影响因子：
7.7
作者：
Ju YS;Alexandrov LB;Gerstung M;Martincorena I;Nik-Zainal S;Ramakrishna M;Davies HR;Papaemmanuil E;Gundem G;Shlien A;Bolli N;Behjati S;Tarpey PS;Nangalia J;Massie CE;Butler AP;Teague JW;Vassiliou GS;Green AR;Du MQ;Unnikrishnan A;Pimanda JE;Teh BT;Munshi N;Greaves M;Vyas P;El-Naggar AK;Santarius T;Collins VP;Grundy R;Taylor JA;Hayes DN;Malkin D;ICGC Breast Cancer Group;ICGC Chronic Myeloid Disorders Group;ICGC Prostate Cancer Group;Foster CS;Warren AY;Whitaker HC;Brewer D;Eeles R;Cooper C;Neal D;Visakorpi T;Isaacs WB;Bova GS;Flanagan AM;Futreal PA;Lynch AG;Chinnery PF;McDermott U;Stratton MR;Campbell PJ
通讯作者：
Campbell PJ
DOI：
10.1098/rsbl.2003.0025
发表时间：
2003-08-07
影响因子：
4.7
作者：
Hebert, PDN;Ratnasingham, S;deWaard, JR
通讯作者：
deWaard, JR
影响因子：
5.2
作者：
Baker, Kathryn T.;Nachmanson, Daniela;Risques, Rosa Ana
通讯作者：
Risques, Rosa Ana